Recurrent pulmonary symptoms in immunocompromised (IC) patients are a common problem, and they pose diagnostic and therapeutic challenges. Repeat FOB is often performed as it is relatively safe, and more invasive procedures may be risky or contra-indicated. The purpose of this study was to evaluate the diagnostic and therapeutic efficacies of repeat FOB in IC patients. A retrospective chart review was performed for all IC patients undergoing repeat FOB in our department from 1/1/87 through 6/3092. Patients were classified as having either "persistent" pulmonary disease (dz) (as documented, and with repeat FOB performed within 3) days of initial FOB), or "new" dz (as documented, and all repeat FOB performed after 30 days from the initial FOB). In patients with HIV infection, a new diagnosis was found in 3/15 repeat FOB (20%) with new dz and 3/25 (12%) with persistent dz (p=NS); change in therapy was initiated in 7/15 repeat FOB (47%) with new dz, and 8/25 (32%) with persistent dz (p=NS). In hematologic/oncologic disorders, a new diagnosis was found in 6/10 repeat FOB (60%) with new dz, and in 7/32 (22%) with persistent dz (p=0.03); a change in therapy was initiated in 7/10 repeat FOB (70%) with new dz, and in 13/32 (41% with persistent dz (p=.11). In patients with other immunocompromised conditions, a new diagnosis was found in 1/9 repeat FOB (11%) with new dz, and 4/12 (33%) with persistent dz (p=NS); a change in therapy was initiated in 3/9 repeat FOB (33%) with new dz, and in 10/12 (83%) with persistent dz (p=0.02). In conclusion, the diagnostic yield to repeat FOB in patients with HIV infection is equally effective in the presence of new or persistent dz; in patients with hematologic/oncologic disorders and new dz, repeat FOB is more likely to establish a new diagnosis; and in patients with other immunocompromised conditions, repeat FOB may be useful in guiding therapy.